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ID PMID Title PublicationDate abstract
25389048 Intensive intervention can lead to a treatment holiday from biological DMARDs in patients 2014 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate (MTX), a synthetic disease-modifying anti-rheumatic drug (sDMARD) and biological DMARDs (bDMARDs) has revolutionized treatment of RA and clinical remission or low disease activity (LDA) are now realistic targets, achieved by a large proportion of RA patients. We are now in a position to evaluate if it is possible to maintain remission or LDA while at the same time reducing the burden of treatment on the patient and healthcare system. Data are emerging from large, well-conducted studies designed to answer this question, shedding light on which patient populations and treatment algorithms can survive treatment discontinuation or tapering with low risk of disease flare. For early RA, approximately half of early RA patients could discontinue TNF-targeted bDMARDs without clinical flare and functional impairment after obtaining clinical remission by bDMARDs with MTX. In contrast, for established RA, fewer patients sustained remission or LDA after the discontinuation of bDMARDs and "deep remission" at the discontinuation was a key factor to maintain the treatment holiday of bDMARDs. Thus, this article provides a brief outline on withdrawing or tapering bDMARDs once patients have achieved remission or LDA in RA.
24579884 Glucocorticoid metabolism in rheumatoid arthritis. 2014 May Endogenous glucocorticoids are implicated in the development and resolution of inflammation. Until recently it was thought that these glucocorticoids arose primarily from the adrenal gland. However, it is now known that several cell types can generate active glucocorticoids within their cytoplasm through expression of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. In a more limited range of cell types, glucocorticoids can be inactivated by the related 11β-HSD2 enzyme. Both enzymes are regulated by inflammation in various settings. In rheumatoid arthritis, 11β-HSD activity is present in the inflamed synovium and appears to influence articular and extraarticular disease processes. The generation of active glucocorticoids in the synovium is strongly linked to the level of inflammation. This local production of glucocorticoids is likely to have paracrine consequences and could underpin inflammation-associated bone loss. The role of 11β-HSD enzymes in the severity and persistence of inflammatory arthritis in a clinical setting is currently being explored.
25407530 Acquiring chondrocyte phenotype from human mesenchymal stem cells under inflammatory condi 2014 Nov 17 An inflammatory milieu breaks down the cartilage matrix and induces chondrocyte apoptosis, resulting in cartilage destruction in patients with cartilage degenerative diseases, such as rheumatoid arthritis or osteoarthritis. Because of the limited regenerative ability of chondrocytes, defects in cartilage are irreversible and difficult to repair. Mesenchymal stem cells (MSCs) are expected to be a new tool for cartilage repair because they are present in the cartilage and are able to differentiate into multiple lineages of cells, including chondrocytes. Although clinical trials using MSCs for patients with cartilage defects have already begun, its efficacy and repair mechanisms remain unknown. A PubMed search conducted in October 2014 using the following medical subject headings (MeSH) terms: mesenchymal stromal cells, chondrogenesis, and cytokines resulted in 204 articles. The titles and abstracts were screened and nine articles relevant to "inflammatory" cytokines and "human" MSCs were identified. Herein, we review the cell biology and mechanisms of chondrocyte phenotype acquisition from human MSCs in an inflammatory milieu and discuss the clinical potential of MSCs for cartilage repair.
24388126 Effectiveness of a group-based intervention to change medication beliefs and improve medic 2014 Mar OBJECTIVE: To assess the effect of a group-based intervention on the balance between necessity beliefs and concern beliefs about medication and on medication non-adherence in patients with rheumatoid arthritis (RA). METHODS: Non-adherent RA patients using disease-modifying anti-rheumatic drugs (DMARDs) were randomized to an intervention or control arm. The intervention consisted, amongst others, of two motivational interviewing-guided group sessions led by the same pharmacist. Control patients received brochures about their DMARDs. Questionnaires were completed up to 12 months follow-up. RESULTS: 123 patients (mean age: 60 years, female: 69%) were randomized. No differences in necessity beliefs and concern beliefs about medication and in medication non-adherence were detected between the intervention and control arm, except at 12 months' follow-up: participants in the intervention arm had less strong necessity beliefs about medication than participants in the control arm (b: -1.0 (95% CI: -2.0, -0.1)). CONCLUSION: This trial did not demonstrate superiority of our intervention over the control arm in changing beliefs about medication or in improving medication adherence over time. PRACTICE IMPLICATIONS: Absent intervention effects might have been due to, amongst others, selection bias and a suboptimal treatment integrity level. Hence, targeting beliefs about medication in clinical practice should not yet be ruled out.
23705017 Influence of adult height on rheumatoid arthritis: association with disease activity, impa 2013 OBJECTIVES: To investigate whether normal variation of adult height is associated with clinical characteristics in rheumatoid arthritis (RA), including disease activity (DAS28), impairment of joint function (mechanical joint score, MJS) and overall disability (health assessment questionnaire, HAQ). METHODS: A cohort (134 males, 287 females) of consecutively recruited RA patients of Northern European origin was studied. Height, weight and demographic information were obtained. A core set of disease measurements, including DAS28, MJS and HAQ, were recorded at baseline, 12 and 24 months. Other clinical variables (e.g. disease duration, IgM rheumatoid factor, antibodies to cyclic citrullinated peptide, C-reactive protein, erythrocyte sedimentation rate) were recorded at baseline. Socioeconomic status, smoking status, comorbid condition, other autoimmune conditions and drug therapy were also recorded. Associations were analyzed using univariate statistics and multivariate linear regression models. Mediation tests were also carried out for evaluating the relationship between gender, height and disease measures. RESULTS: In males, height was inversely associated with DAS28, MJS and HAQ (at baseline and over 24 months) independent of other factors (e.g. weight, body mass index, age, disease duration, osteoporosis, autoantibodies, erosive disease, joint replacement, steroid use, smoking status, socioeconomic status and comorbid disease). In females, a similar trend was seen but the relationships were non significant. In the whole population, the association of female gender with more active disease and poor function disappeared after adjustment for height. Mediation analysis indicated that height served as a full mediator in the relationship of gender with disease activity and overall disability. Confirmation of these findings was demonstrated in a second RA population (n = 288). CONCLUSION: Adult height is inversely associated with disease activity, impairment of joint function and overall disability in RA, particularly in males. The association of female sex with more severe disease activity and disability appears to be mediated by smaller stature.
24551146 Symptoms, the nature of fibromyalgia, and diagnostic and statistical manual 5 (DSM-5) defi 2014 PURPOSE: To describe and evaluate somatic symptoms in patients with rheumatoid arthritis (RA) and fibromyalgia, determine the relation between somatization syndromes and fibromyalgia, and evaluate symptom data in light of the Diagnostic and Statistical Manual-5 (DSM-5) criteria for somatic symptom disorder. METHODS: We administered the Patient Health Questionnaire-15 (PHQ-15), a measure of somatic symptom severity to 6,233 persons with fibromyalgia, RA, and osteoarthritis. PHQ-15 scores of 5, 10, and 15 represent low, medium, and high somatic symptom severity cut-points. A likely somatization syndrome was diagnosed when PHQ-15 score was ≥10. The intensity of fibromyalgia diagnostic symptoms was measured by the polysymptomatic distress (PSD) scale. RESULTS: 26.4% of RA patients and 88.9% with fibromyalgia had PHQ-15 scores ≥10 compared with 9.3% in the general population. With each step-wise increase in PHQ-15 category, more abnormal mental and physical health status scores were observed. RA patients satisfying fibromyalgia criteria increased from 1.2% in the PHQ-15 low category to 88.9% in the high category. The sensitivity and specificity of PHQ-15≥10 for fibromyalgia diagnosis was 80.9% and 80.0% (correctly classified = 80.3%) compared with 84.3% and 93.7% (correctly classified = 91.7%) for the PSD scale. 51.4% of fibromyalgia patients and 14.8% with RA had fatigue, sleep or cognitive problems that were severe, continuous, and life-disturbing; and almost all fibromyalgia patients had severe impairments of function and quality of life. CONCLUSIONS: All patients with fibromyalgia will satisfy the DSM-5 "A" criterion for distressing somatic symptoms, and most would seem to satisfy DSM-5 "B" criterion because symptom impact is life-disturbing or associated with substantial impairment of function and quality of life. But the "B" designation requires special knowledge that symptoms are "disproportionate" or "excessive," something that is uncertain and controversial. The reliability and validity of DSM-5 criteria in this population is likely to be low.
23401426 Ambient air pollution exposures and risk of rheumatoid arthritis. 2013 Jul OBJECTIVE: Environmental factors may play a role in the development of rheumatoid arthritis (RA). We previously observed increased RA risk among women living closer to major roads (a source of air pollution). Herein, we examined whether long-term exposures to specific air pollutants were associated with RA risk among women in the Nurses' Health Study (NHS). METHODS: The NHS is a large US cohort of female nurses followed up prospectively every 2 years since 1976. We studied 111,425 NHS participants with information on air pollution exposures as well as data concerning other lifestyle and behavioral exposures and disease outcomes. Outdoor levels of different size fractions of particulate matter (PM10 and PM2.5 ) and gaseous pollutants (SO2 and NO2 ) were predicted for all available residential addresses using monitoring data from the US Environmental Protection Agency. We examined the association of time-varying exposures 6 and 10 years before each questionnaire cycle and cumulative average exposure with the risk of RA, seronegative (rheumatoid factor and anti-citrullinated peptide antibody negative) RA, and seropositive RA. RESULTS: Over the 3,019,424 person-years of followup, 858 incident RA cases were validated by medical record review by 2 board-certified rheumatologists. Overall, we found no evidence of increased risk of RA, seronegative RA, or seropositive RA with exposure to the different pollutants and little evidence of effect modification by socioeconomic status or smoking status, geographic region, or calendar period. CONCLUSION: In this group of socioeconomically advantaged middle-aged and elderly women, adult exposures to air pollution were not associated with an increased RA risk.
23819216 [Effect of different types of moxibustion intervention on expression of inflammatory cytok 2013 Apr OBJECTIVE: To observe the effect of different moxibustion intervention on expression of interleukin-1 (IL-l) and tumor necrosis factor-alpha (TNF-alpha) in the synovial fluid of hind-knee joint in rheumatoid arthritis (RA) rabbits. METHODS: Forty Japanese big-ear white rabbits (half male and half female) were randomized into normal control, RA model, direct-moxibustion, ginger-partitioned moxibustion and warm moxibustion groups (n= 8). RA model was established by injection of Freund's Complete Adjuvant (0. 5 mL/kg) into the articular cavities of the rabbits' bilateral hind-limbs. Moxibustion intervention was applied to unilateral "Shenshu" (BL 23) and "Zusanli"(ST 36) regions alternatively for 20 min from the 7th day on after modeling, once daily for 3 weeks except Sundays. The circumference of the hindlimb-knee joint was measured using a tape measure and the contents of IL-1 and TNF-alpha in the synovial fluid of articular cavities were detected by ELISA. RESULTS: In comparison with the normal control group, the circumference values of the bilateral hind-knee joints, and the contents of IL-1 and TNF-alpha in the synovial fluid of articular cavities in the model group were significantly increased (P<0. 01). After the moxibustion treatment, compared with the model group, the circumference values of the bilateral hind-knee joints, and IL-1 and TNF-alpha contents of the synovial fluid in the warm moxibustion, direct moxibustion and ginger-partitioned moxibustion groups were remarkably reduced (P<0.01, P<0.05). The effects of the ginger-partitioned group were significantly superior to those of both warm moxibustion and direct moxibustion groups in decreasing the swelled hind-knee joint circumference on day 21 after the treatment and down-regulating synovial fluid inflammatory cytokines IL-1 and TNF-alpha levels (P<0. 05). CONCLUSION: Warm, direct and ginger-separated moxibustion interventions all can reduce inflammatory reactions of the knee-joint and suppress inflammatory cytokine IL-1 and TNF-alpha levels of the synovial fluid in RA rabbits, which may contribute to its effect in improving RA in clinic. The therapeutic effect of ginger-partitioned muxibustion intervention is apparently better.
23492974 Lumbar scoliosis in rheumatoid arthritis: epidemiological research with a DXA cohort. 2013 Mar 15 STUDY DESIGN: A retrospective cross-sectional study. OBJECTIVE: The aim of this study was to identify the prevalence of and risk factors for lumbar scoliosis in patients with rheumatoid arthritis (RA) using lumbar images obtained from dual-energy x-ray absorptiometry (DXA). SUMMARY OF BACKGROUND DATA: The prevalence of lumbar scoliosis in the normal adult population has been reported, but that in patients with RA remains unclear. METHODS: Subjects comprised 241 patients with RA who underwent annual DXA. Cobb angles of the lumbar spine were measured by lumbar anteroposterior DXA and the prevalence of lumbar scoliosis (curvature ≥10°) was calculated. Correlations between lumbar scoliosis and potential risk factors (age, sex, duration of RA, T score of lumbar spine and hip, medications for RA [daily predonisolone dose, use of biological agents] and osteoporosis, disease activity score-C-reactive protein, progression stage and functional classification of RA, and severity of hand deformity were analyzed. RESULTS: The prevalence of lumbar scoliosis in patients with RA was 32.0%. Mean Cobb angle was 7.1º ± 5.5º among all subjects, compared with 13.6º ± 4.4º (range, 10º-32º) among subjects with scoliosis. Subjects with scoliosis were significantly older (67.8 yr) than those without (61.6 yr, P < 0.0001). The daily prednisolone dose was significantly higher in subjects with scoliosis (4.14 mg) than in those without (3.46 mg, P = 0.0389). The T score of the hip was significantly smaller in subjects with scoliosis (-1.79) than in those without (-1.26, P = 0.0005). A multivariate logistic regression analysis revealed age as the sole risk factor for lumbar scoliotic changes in patients with RA (odds ratio, 1.068; 95% confidence interval, 1.031-1.107; P = 0.0003). CONCLUSION: The prevalence of lumbar scoliosis in patients with RA was 32.0%, about 3- or 4-times higher than its prevalence as obtained from previous reports of DXA cohorts irrespective of RA. Increased age represented an independent risk factor for lumbar scoliosis in patients with RA. LEVEL OF EVIDENCE: 4.
24632598 Association of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in pat 2014 BACKGROUND: Mannan-binding lectin-associated serine protease 2 (MASP-2) is a key protein of the lectin pathway of complement. MASP-2 levels have been associated with different polymorphisms within MASP2 gene as well as with the risk for inflammatory disorders and infections. Despite its clinical importance, MASP-2 remains poorly investigated in rheumatoid arthritis (RA). METHODS: In this case-control study, we measured MASP-2 serum levels in 156 RA patients, 44 patient relatives, and 100 controls from Southern Brazil, associating the results with nine MASP2 polymorphisms in all patients, 111 relatives, and 230 controls genotyped with multiplex SSP-PCR. RESULTS: MASP-2 levels were lower in patients than in controls and relatives (medians 181 vs. 340 or 285 ng/ml, respectively, P<0.0001). Conversely, high MASP-2 levels were associated with lower susceptibility to RA and to articular symptoms independently of age, gender, ethnicity, smoking habit, anti-CCP and rheumatoid factor positivity (OR = 0.05 [95%CI = 0.019-0.13], P<0.0001 between patients and controls; OR = 0.12, [95%CI = 0.03-0.45], P = 0.002 between patients and relatives; OR = 0.06, [95%CI = 0.004-0.73], P = 0.03 between relatives with and without articular symptoms). MASP2 haplotypes *2A1 and *2B1-i were associated with increased susceptibility to RA (OR = 3.32 [95%CI = 1.48-7.45], P = 0.004). Deficiency-causing p.120G and p.439H substitutions were associated with five times increased susceptibility to articular symptoms in relatives (OR = 5.13 [95%CI = 1.36-20.84], P = 0.02). There was no association of MASP-2 levels or MASP2 polymorphisms with autoantibodies, Sjögren's syndrome, nodules and functional class. CONCLUSIONS: In this study, we found the first evidence that MASP-2 deficiency might play an important role in the development of RA and articular symptoms among relatives of RA patients.
24310684 [Association between insomnia and rheumatoid arthritis in elderly]. 2013 Aug This study aimed to assess symptoms of insomnia in elderly residents in the community and its association with rheumatoid arthritis. Descriptive and cross-sectional study, part of a multicentre research project entitled Fragility in Brazilian elderly . A total number of 689 elderly (68.9% female, average age of 72.2 years) were interviewed using a questionnaire on sociodemographic data and clinical conditions. Two tools to identify symptoms of insomnia (the Nottingham Health profile) and to screen cognitive impairment (Mini Mental State Examination) were also applied. For data analysis, we used descriptive statistical techniques and multiple logistic regression, considering a 5% significance level. The association between insomnia symptoms and rheumatoid arthritis was found to be significant in the multivariate analysis; other associated factors were a very poor subjective evaluation of health, being retired, and the presence of depression. Health professionals should investigate carefully the sleep quality in elderly with rheumatoid arthritis, considering its high prevalence in this population.
25222755 The relationships between serum sclerostin, bone mineral density, and vascular calcificati 2014 Dec CONTEXT: Recent data indicate that the secreted glycoprotein sclerostin may be involved in vascular calcification (VC). OBJECTIVE: The objective of the study was to establish whether serum sclerostin levels are associated with VC in patients with rheumatoid arthritis (RA). DESIGN: This was a cross-sectional study. SETTING: The study was conducted with ambulatory care. PATIENTS: We compared 75 RA patients with 75 age- and gender-matched control participants. INTERVENTION: Coronary artery calcification (CAC) and abdominal aortic calcification (AAC) scores were evaluated by computed tomography. MAIN OUTCOME MEASURE: Serum sclerostin levels (determined with an ELISA) were assessed. A statistical analysis was performed to identify the determinants of serum sclerostin and VC. RESULTS: AAC and CAC were more prevalent and more severe in patients with RA than in controls. Higher levels of AAC (P = .02) and a higher lumbar bone mineral density (BMD; P = .03) were identified as independent determinants of higher serum sclerostin levels in RA patients, whereas male gender (P = .03), higher lumbar BMD (P < .0001), and low estimated glomerular rate (P < .001) were identified as determinants in controls. In RA patients, a multivariate logistic regression analysis indicated that older age [P < .01, with an odds ratio (OR) per year 1.10] and male gender (P = .02, OR 6.79) were independent determinants of CAC and that older age (P < .001, OR 1.16) were independent determinants of AAC. In controls, the independent determinants were older age (P < .01, OR 1.19), hypertension (P < .01, OR 7.31), and lumbar BMD (P = .03, OR per 30 mg/cm(2) increment of 1.14) for CAC and older age (P = .01, OR 1.11) for AAC. CONCLUSIONS: Serum sclerostin levels were significantly and independently associated with AAC in RA patients.
23683943 Autoimmunity in rheumatoid arthritis: citrulline immunity and beyond. 2013 Rheumatoid arthritis (RA) represents a disease where we have recently acquired new knowledge on etiology and molecular pathogenesis, by combining data from studies on genetic end environmental determinants of disease with molecular and cellular immunology. This combined approach has provided insights into the heterogeneous nature of the clinical syndrome we call RA, and the subdivisions into different functional disease subsets now permit a better use of molecular immunology in contexts where genotypes and environmental triggers are defined. In this chapter, we discuss a series of different autoimmunities described in RA, with an initial emphasis on immunity to autoantigens that have been posttranslationally modified by citrullination. We then discuss a series of unresolved issues and challenges related both to the citrulline immunity and to other immune events in RA. Our perspective is that current studies on genes, environment, and immunity in this disease provides us with a great outlook to investigate interesting general aspects of autoimmunity and development of human autoimmune disease--in addition to the opportunity to better understand, prevent, and ultimately treat RA.
24671501 A randomized, double-blind, and placebo-controlled multicenter clinical trial of a novel c 2014 Nov To assess the clinical efficacy as well as safety profiles of Leining, a novel cytotoxic T-lymphocyte antigen-4 fusion protein, versus placebo in the treatment of Chinese active rheumatoid arthritis (RA) patients with an inadequate clinical response to methotrexate (MTX). In this 24-week, randomized, double-blind, placebo-controlled multicenter study, a total of 440 Chinese patients with active RA with an inadequate response to MTX were randomly assigned to receive Leining (10 mg/kg) or placebo. Clinical response was assessed using the American College of Rheumatology 20 % improvement criteria ACR20, ACR50, and ACR70, with ACR20 as the primary major endpoints. Disease activity scores in 28 joints with erythrocyte sedimentation rate assessment (DAS28-ESR) were used to evaluate disease activity. After 24 weeks of treatment, significantly more patients in Leining group achieved ACR20 response than those in placebo group (70.61 vs. 46.36 %; p < 0.001). Similarly, ACR50 and ACR70 responses of Leining group were significantly higher than those of placebo group (40.30 vs. 22.73 %; p < 0.001 and 16.67 vs. 7.27 %; p < 0.05, respectively). DAS28-ESR in Leining group was significantly reduced compared to that in placebo group, with greater clinically meaningful (>1.2 unit) improvement (54.85 vs. 29.09 %, p < 0.05). Both the rates of remission (DAS28-ESR < 2.6) and low disease activity (DAS28-ESR < 3.2) were greater in the Leining group than those in the placebo group (12.42 vs. 2.73 %; p < 0.05 and 15.45 vs. 2.73 %; p < 0.05 respectively). The overall incidence of adverse events was similar in both Leining and placebo groups. No neutralizing antibodies were detected. Leining demonstrated clinically meaningful efficacy compared with placebo in Chinese patients with active RA despite MTX therapy. Administration of Leining in combination with MTX for 24 weeks was well tolerated.
24589014 Changes in peripheral blood B cell subsets at diagnosis and after treatment with disease-m 2015 May OBJECTIVE: To assess variation in peripheral blood B lymphocyte subsets in rheumatoid arthritis (RA). METHODS: B lymphocyte subsets in disease-modifying anti-rheumatic drug (DMARD)-naïve patients with RA (n = 30), patients with RA treated with DMARDs (n = 73) and healthy controls (n = 46) were analyzed by flow cytometry. Total B cells, total memory B cells, immunoglobulin M (IgM) memory B cells, switched memory B cells, non-switched memory B cells, CD21lo B cells, transitional B cells and plasmablasts were measured. Correlation with clinical and laboratory parameters was performed. RESULTS: Total memory B cells, IgM memory B cells and non-switched memory B cells were reduced in RA patients at diagnosis compared to controls (P < 0.05). In patients with treated RA, there was a further reduction of total B cells, CD21lo cells, transitional B cells and plasmablasts, compared to controls (P < 0.05). The reduction in absolute numbers of total B cells, switched memory B cells, CD21lo cells, transitional B cells and plasmablasts in treated RA patients was significant (P < 0.05) even when compared to the DMARD-naïve patients. Only treatment responders (Disease Activity Score < 3.2) had reduced total B cells and absolute numbers of switched and IgM memory B cells (P < 0.05). In patients requiring leflunomide, total memory B cells, IgM memory B cells, non-switched memory B cells and absolute numbers of switched memory B cells were reduced compared with the remainder of the patient group (P < 0.05). CONCLUSION: There is reduction of various B cell subsets in RA patients at diagnosis. Treatment with DMARDs leads to further reduction in additional B cell subsets without correction of the abnormalities. Reduction in individual subsets may predict RA patients requiring more intensive therapy.
25327997 The association of fatigue, comorbidity burden, disease activity, disability and gross dom 2014 Nov OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). METHODS: Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. RESULTS: Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. CONCLUSIONS: Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.
24014495 Interleukin-1 receptor antagonist gene polymorphism and hepcidin in rheumatoid arthritis: 2013 Oct Rheumatoid arthritis (RA) is a systemic autoimmune disease, which is manifested as an inflammatory polyarthritis. Authors aimed to analyze the relationship between serum hepcidin, 25 amino acid protein, concentration and the anemia profiles of RA and to estimate whether it could reflect the disease activity of RA. Also, this study was conducted to explore the linkage between interleukin-1 (IL-1) receptor antagonist gene (IL-1RN) polymorphism, proinflammatory cytokine, and RA. One hundred and eighty five RA patients were enrolled in the study. For all, the following criteria were measured: RA disease activities, anemia profiles, serum concentration of hepcidin using enzyme-linked immunosorbent assay, and DNA samples were used to study genotypes of IL-1RN gene by polymerase chain reaction. Mean concentration of serum pro-hepcidin was (93.6 ± 31.5 ng/mL) in 185 RA patients. An increased frequency of the IL-1RN*1 and IL-1RN*2 alleles was relative to active RA (DAS28 > 5.1) than those with inactive to moderate RA (DAS28 ≤ 5.1). Both hepcidin and IL-1RN gene showed significant correlation with each other as well with RA disease activity parameters and anemia profile. IL-1RN gene was significantly correlated with laboratory anemia profile apart from transferritin. There was a significant difference among pro-hepcidin concentration and IL-1RN frequency regarding patients with anemia of chronic disease and those without. In conclusion, both serum concentration of pro-hepcidin and IL-1RN genotypes frequency reflect the disease activity, regardless of the anemia states in RA patients, thus they may be another potential markers for disease activity of RA.
24779371 Cardiovascular case fatality in rheumatoid arthritis is decreasing; first prospective anal 2014 Apr 29 BACKGROUND: Previous studies found increased case fatality after myocardial infarction and more frequent sudden death in RA patients compared to non-RA subjects. The RA associated CV risk might be explained by the combined effects of chronic systemic inflammation and increased lifestyle associated cardiovascular risk factors, and modified by the use of medication such as non steroidal anti-inflammatory drugs, corticosteroids and disease modifying anti-rheumatic drugs. Trends in case fatality rate in RA after the introduction of potent anti-inflammatory biologic therapies and treat-to-target treatment strategies aiming at remission are not known. This study was performed to examine the cardiovascular fatality rate in current low disease activity RA, and to evaluate trends in RA associated CV case fatality over time. METHODS: Prospective study to determine the incidence of fatal and nonfatal CV events in 480 RA patients included in the ACT-CVD cohort between February 2009 and December 2011. Patients with prior CV disease were excluded. Cox regression analysis was performed to determine CV event risk and contributing risk factors over time. The results of the cohort analysis were put into the context of a review of the literature to evaluate trends in RA associated CV fatality rate over time. RESULTS: The study included 480 RA patients, 72.3% female with median disease duration of 4.2 years, 72.1% being in clinical remission (Disease Activity Score in 28 joints). During a mean follow up of 2.9 years 29 patients (6%) experienced a first CV event, 2 fatal and 27 non-fatal, corresponding to a 6.9% case fatality rate. Comparison with previous studies in cohorts with successive enrolment periods shows a trend towards a decrease in CV case fatality in RA from 52.9% in 1998 to 6.9% in our study. CONCLUSION: CV case fatality in current low disease activity RA is importantly lower than in previous studies, and a trend towards decreasing CV fatality in RA is suggested.
24880982 Does periodontal treatment influence clinical and biochemical measures for rheumatoid arth 2014 Oct OBJECTIVE: Periodontitis is a potential risk factor for rheumatoid arthritis (RA). This systematic review considers the evidence for whether non-surgical treatment of periodontitis in RA patients has any effect on the clinical markers of RA disease activity. METHODS: MEDLINE/PubMed, CINAHL, DOSS, Embase, Scopus, Web of Knowledge, MedNar, Lilacs and ProQuest Theses and Dissertations were searched till September 2013 for quantitative studies examining the effect of non-surgical periodontal treatment on disease activity of RA. The following were the inclusion criteria: (1) patients diagnosed with both RA and chronic periodontitis, aged 30 years or older; (2) no antibiotics in the past 3 months or periodontal treatment in the past 6 months; (3) non-surgical periodontal therapy; (4) age- and gender-matched control group; (5) measures of RA activity and (6) published in English. RESULTS: Five studies met the inclusion criteria. Non-surgical periodontal treatment was associated with significant reductions in erythrocyte sedimentation rate and a trend towards a reduction in TNF-α titres and DAS scores. There was no evidence of an effect on RF, C-reactive protein, anti-cyclic citrullinated protein antibodies and IL-6. CONCLUSIONS: Based on clinical and biochemical markers, non-surgical periodontal treatment in individuals with periodontitis and RA could lead to improvements in markers of disease activity in RA. All studies had low subject numbers with the periods of intervention no longer than 6 months. Larger studies are required to explore the effect of non-surgical periodontal treatment on clinical indicators of RA, using more rigorous biochemical and clinical outcome measures as well as giving consideration to potential confounding factors of co-morbidity.
23509709 Taenia crassiceps infection does not influence the development of experimental rheumatoid 2013 It was previously reported by our group that infection with Taenia crassiceps reduces incidence and severity of inflammatory and autoimmune experimental diseases like type 1 diabetes and experimental autoimmune encephalomyelitis. In this research, we set out to study whether infection with T. crassiceps would affect the development of experimental rheumatoid arthritis (RA). We found that mice infected with the parasite and induced with experimental RA showed similar clinical scores as the noninfected experimental RA group; systemic cytokines were not affected while anti-CII Abs were higher in the infected group. Histological evaluation showed damage in both infected and noninfected experimental RA-induced groups and although some surface molecules such as PDL-2 and MR which are associated with immunomodulatory mechanisms were upregulated in the infected and RA-induced group as compared to the noninfected RA group, they did not exert any changes in the outcome of experimental RA. Thus, we determined that infection with T. crassiceps does not influence the outcome of experimental RA.